This study is a joint effort of the departments of Rehabilitation Medicine, Pharmacology, and the Center for Biomedical Engineering. Despite the high prevalence and cost of pressure sores (PS), little scientific study has been directed towards the biochemical and molecular mechanisms of ulcer development, thus hampering effective treatment. Clinical studies on PS are difficult to assess because they are often qualitative, empirical, and uncontrolled. Our computer-controlled animal model allows for rigorous scientific analysis and evaluation of proposed PS treatments and preventatives. This system allows us to investigate the relationship between ischemia/reperfusion (IR) injury and free radical (FR) production by relating the biochemical events to the noninvasive measurement of blood flow utilizing a laser Doppler flow meter. Pressure ulcers are thought to develop as a result of IR/insult of the underlying subcutaneous tissue (muscle and/or adipose tissue). The current proposal is designed to directly determine the relationship between pressure/ischemia duration and frequency and the ultimate development of PS. Measurement of free radical (FR) production will verify the involvement of FR in the pathophysiology of PS development. FR spin- trapping compounds and other agents will be evaluated as to their ability to limit or prevent the development of PS. Our investigation of molecular causes of PS will continue with the testing of our hypothesis that apoptosis (programmed cell death) may play a significant role in the formation of decubitus ulcers. FR, apoptosis, and PS are intimately associated with cell death. If apoptosis is identified, several treatments would be implicated (i.e. use of inhibitors of protein and/or RNA synthesis).